Cavendish equalled the all-time record for stage wins at the Tour last year, matching Eddy Merckx's tally of 34 victories - which had stood since 1975.
The Manxman looked to have boosted his hopes of making the eight-man team by triumphing at the British National Road Championship on Sunday, having featured at the Giro d'Italia for the first time in nine years.
But Fabio Jakobsen has a superior record in sprints this season, with 10 wins compared to Cavendish's five, and the Dutchman has got the nod for Le Tour, which starts in Copenhagen on Friday.
Kasper Asgreen, Andrea Bagioli, Mattia Cattaneo, Tim Declercq, Mikkel Honore, Yves Lampaert and Michael Morkov are the other seven riders to be picked.
Cavendish and Florian Senechal were named as first-reserve riders on Monday, while Alaphilippe was not included.
"Over 3,300 kilometres and more than 55,000 meters of elevation promise to make for a tough race," Quick-Step Alpha Vinyl sports director Tom Steels said.
"After the first ITT, we have two other days in Denmark, which should be for the sprinters, that is if we won't have any echelons.
"The cobblestones stage will be a very tricky stage, as everyone will want to be at the front, and after this we'll have a lot of climbing, with many iconic ascents of the Tour de France.
"The climbers will get plenty of opportunities at this edition, unlike the sprinters, who'll have to fight in many of the stages against the time limit.
"Overall, the race has something for everyone, and that's why we are going there with a balanced team."
Alaphilippe was widely expected to be picked after racing in the French National Championships two months after his Liege–Bastogne–Liege crash, but there is no place for the popular 30-year-old.
"Concerning our reserves, we must stress out that they showed a lot of professionalism, continued to train and remained focused in these past couple of weeks, and even brought two victories at the Nationals," Steels added.
"The decision to leave Julian home was a very difficult one, as he is one of the team's most emblematic riders and we wrote so many great moments together at the Tour.
"Julian worked hard to get back into shape after what happened to him in Liege, but it is felt that for a rider like him it's always important to be on top of his game and be able to compete with the best riders of the peloton in a race like Le Tour.
"That's why we decided to give him more time to recover and build back his condition, so that he can be at 100 per cent for the second part of the season."
Cavendish last featured in the race in 2013, topping the points classification after winning five stages.
The legendary sprinter has 15 stage wins in five previous appearances in the race, and will be hoping to replicate his successful comeback at last year's Tour de France, where he matched Eddy Merckx's career record of 34 stage victories, which had stood since 1975, after a three-year absence from the race.
As his team confirmed Cavendish's participation on Twitter, directeur sportif Davide Bramati said he is excited about the 36-year-old's chances of further success.
"We go to the Giro d’Italia with a lot of motivation. We have a good team at the start, with Mark as our man for the flat," Bramati said in a team statement.
"He has won a lot of stages at the Giro, and he can rely on many strong riders to support and guide him in the hectic bunch sprints.
"For the other stages, we'll just take it one day at a time, fight for every opportunity and see what we can do. We know that it won't be an easy three weeks, it never is, but we will try to do our best, because it's in our nature."
Cavendish's selection for the three-week race, which begins in Budapest on May 6 and finishes in Verona on May 29, does, however, make another appearance in the Tour de France appear to be unlikely this year, with Dutch sprinter Fabio Jakobsen expected to get the nod.
The 36-year-old has been in good form in 2022, becoming the first British rider to win the Milano-Torino one-day race and picking up three race victories since the turn of the year.
The incident happened at the Tour of Poland in August, with Groenewegen deviating from his line and nudging Dutch compatriot Jakobsen during a sprint for the finish.
Jumbo-Visma suspended Groenewegen from competing until the UCI made a ruling over any sanctions, with the governing body announcing its decision to impose a backdated ban on Wednesday.
"The UCI referred the case against the rider, who acknowledged that he deviated from his line and committed a violation of the UCI Regulations," read a statement.
"The rider collaborated with the investigation and accepted to serve a period of suspension until 7 May 2021, corresponding to a period of nine months from the date of the incident.
"The rider also accepted to take part in a number of events to the benefit of the cycling community."
Jakobsen spent a week in intensive care and has undergone facial surgery, with the 24-year-old on a long road to recovery.
Groenewegen, who had already apologised for his actions, posted on Instagram following the ruling.
"The crash in the first stage of the Tour of Poland will forever be a black page in my career," he said.
"During the sprint I deviated from my line. I am sorry, because I want to be a fair sprinter. The consequences were very unfortunate and serious.
"I am very aware of that and I hope this has been a wise lesson for every sprinter.
"I follow the news of Fabio's recovery very closely. I can only hope that one day he will return completely."
Deceuninck-QuickStep rider Jakobsen was in a serious but stable condition in a Katowice hospital after undergoing facial surgery, with doctors intending to wake the 23-year-old on Thursday.
Jakobsen was airlifted to hospital on Wednesday after fellow Dutchman Groenewegen appeared to nudge him into the barriers in a high-speed sprint finish on the opening stage of the race.
Jumbo-Wisma rider Groenewegen was disqualified and strongly condemned by governing body the Union Cycliste Internationale (UCI) for his "dangerous behaviour".
Groenewegen made a first public statement on Thursday, saying he felt for Jakobsen.
He posted on Twitter: "I hate what happened yesterday. I can't find the words to describe how sorry I am for Fabio and others who have fallen or been hit.
"At the moment, the health of Fabio is the most important thing. I think about him constantly."
Jumbo-Wisma issued an apology on Wednesday and said an internal review would take place.
"Our thoughts go out to Fabio Jakobsen and other people involved in today's terrible crash in the Tour of Poland. Crashes like these should not happen," the team tweeted.
"We offer our sincere apologies and we will discuss internally what has happened before we may make any further statement."
Jakobsen was sent over the barriers during a sprint finish with Dylan Groenewegen, who was subsequently disqualified by the UCI for appearing to nudge his competitor.
Several other riders were injured after crashing as the barriers split and flew across the road, with Jakobsen airlifted to hospital where he was placed into an induced coma.
Deceuninck – Quick Step have now provided an update on their rider's condition.
"Fabio Jakobsen's situation is serious but at the moment he is stable," a statement from the team read.
"Diagnostic tests did not reveal brain or spinal injury, but because of the gravity of his multiple injuries, he is still kept in a comatose condition and has to remain closely monitored in the following days at the Wojewodzki Szpital in Katowice.
"Further information will be made available in the course of the coming hours. Meanwhile, we would like to thank you for your heartwarming support."
Prior to Deceuninck – Quick Step's update, UCI strongly condemned the actions of Team Jumbo-Wisma rider Groenewegen.
Jumbo-Wisma posted on Twitter to apologise for the incident and said an internal review will be taking place.
"Our thoughts go out to Fabio Jakobsen and other people involved in today's terrible crash in the Tour of Poland. Crashes like these should not happen," it read.
"We offer our sincere apologies and we will discuss internally what has happened before we may make any further statement. #TDP20."
Jakobsen was placed in an induced coma after being airlifted to Wojewodzki Szpital in Katowice on Wednesday following the smash at the end of stage one.
Dylan Groenewegen was disqualified and strongly condemned by governing body the Union Cycliste Internationale (UCI) for "dangerous behaviour", having appeared to nudge his Dutch compatriot into the barriers in a sprint finish.
Tests revealed Jakobsen did not suffer brain or spinal injuries, but he remains in a coma following an operation and doctors will attempt to wake the 23-year-old up later on Thursday.
Deceuninck-QuickStep said in a statement: "Fabio had facial surgery during the night. His situation is stable at the moment and later today the doctors will try to wake Fabio up."
Jumbo-Wisma, Groenewegen's team, issued an apology and said an internal review will take place.
"Our thoughts go out to Fabio Jakobsen and other people involved in today's terrible crash in the Tour of Poland. Crashes like these should not happen," the team tweeted.
"We offer our sincere apologies and we will discuss internally what has happened before we may make any further statement. #TDP20."
Groenewegen won the stage but was later disqualified from the race after Jakobsen was sent careering over the barriers during a sprint finish.
Several other riders were injured after crashing as the barriers split and flew across the road.
Deceuninck-Quick-Step rider Jakobsen was airlifted to hospital, as was a course-side referee, where he was later placed into an induced coma.
A statement from UCI read: "[The UCI] strongly condemns the dangerous behaviour of rider Dylan Groenewegen (Jumbo-Wisma), who sent Fabio Jakobsen (Deceuninck-Quick-Step) into the barriers a few metres from the finish, causing a collective crash at the end of the first stage of the Tour of Poland.
"Groenewegen was disqualified from the race by the commissaires' panel.
"The UCI, which considers the behaviour unacceptable, immediately referred the matter to the Disciplinary Commission to request the imposition of sanctions commensurate with the seriousness of the facts.
"Our Federation is wholeheartedly with the affected riders."
Jumbo-Wisma posted on Twitter to apologise for the incident and said an internal review will be taking place.
"Our thoughts go out to Fabio Jakobsen and other people involved in today's terrible crash in the Tour of Poland. Crashes like these should not happen," it read.
"We offer our sincere apologies and we will discuss internally what has happened before we may make any further statement. #TDP20."
Deceuninck-Quickstep posted: "Our thoughts and prayers are with Fabio Jakobsen. When we have news, we will let you know. Thank you from the bottom of our hearts for your support."
