Medvedev's winning streak was halted at 19 matches by the sensational Alcaraz, who claimed his third Masters 1000 title in style on Sunday.
Alcaraz won 6-3 6-2 in just 72 minutes to return to the summit of the ATP rankings, with Novak Djokovic having been unable to feature in the United States due to his COVID-19 vaccination status.
Medvedev had won three titles in a row – at the Rotterdam Open, Qatar Open and Dubai Tennis Championships, where he beat Djokovic – ahead of competing at Indian Wells, yet proved no match for the imperious Alcaraz, who he had beaten in their only previous meeting, at Wimbledon in 2021.
The Russian had to overcome several hurdles to reach the final, having rolled his ankle in his fourth-round win over Alexander Zverev while he also hurt his thumb in a quarter-final defeat of Alejandro Davidovich Fokina.
Yet despite the trials and tribulations, and his humbling loss in the final, Medvedev was in good spirits.
"I had a pretty toxic relationship here with the courts, a love-hate relationship," Medvedev chuckled. "So I'd like to thank the court!
"I only played on this court. I gave it a hard time so it gave me a hard time also. Rolled the ankle, the thumb... but it gave me the chance to finish the tournament.
"Thanks a lot to this court, I'll definitely be back.
"I really love this tournament, I'll be happy to come back many more years to come and hopefully I can start to love this court and Indian Wells together."
Addressing the crowd, Medvedev quipped: "Sorry I didn't make this final entertaining. I tried, I don't like to lose, but today was unfortunately pretty easy. I hope you still enjoyed it."
Alcaraz is one of only three players to hold a 100 per cent record in multiple ATP Masters 1000 finals, having now won in the finals of the Miami Open, Indian Wells Open and Madrid Open without dropping a set.
"I'd like to congratulate Carlos," said Medvedev. "You already have amazing achievements in your career and I'm sure many more to come.
"Today's one more of them, winning Indian Wells. I also dream of it – maybe next time you'll give me the chance!
"Congrats to you and your team. You're probably the most respectful player on Tour, you probably say hi to 300 people a day. I've rarely seen it!"
Alcaraz returned the plaudits, telling Medvedev he serves as an inspiration to be "better on the court and off the court".
"It has been a really amazing run here, such an amazing experience," the 19-year-old added.
When asked if he had played a near perfect match, Alcaraz told Amazon Prime: "Yes, probably. I played really, really well.
"I made no tactical mistakes, which is really important against Daniil. I would say I was perfect in that way.
"I'm really happy with the way I played, the trophy and of course to be world number one."
While Alcaraz will return to the top of the world on Monday, compatriot and idol Rafael Nadal is set to drop out of the top 10 for the first time since April 2005.