Roger Federer will play the winner of the tie between France's Jo-Wilfried Tsonga and Croatia's Milos Raonic after receiving a bye in the first round.
Novak Djokovic is aiming to lift the trophy at the only one of the Masters 1000 series events that he has never won.
Milos Raonic cranked up the fastest serve of the tournament on Wednesday with a 147mph (236.5km/h) howitzer.
Roger Federer will play for the 98th title of his career on Sunday against Milos Raonic.
Juan Martin del Potro sent his devoted fans home happy Tuesday by powering into the ATP Miami Open quarter-finals with a 6-4, 6-2 triumph over Serbian Filip Krajinovic.
Juan Martin del Potro is looking for his 22nd career and second straight ATP title in a row after winning earlier this month in Acapulco.
Milos Raonic didn't play in Indian Wells last year because of a string of injuries and surgeries that decimated his season.
Milos Raonic was stunned by Lukas Lacko in the first round of the tournament.
The US Open, final Grand Slam of the season, starts on Monday at Flushing Meadows in New York.
Canadian sixth seed Raonic had knocked out Federer in the semi-finals in 2016, a defeat which led the Swiss superstar to shut down the rest of his season to rest a knee injury.
Roger Federer hit his 10,000th career ace in the eighth game of the first set.
Rafael Nadal needed all his trademark grit against Alexander Zverev, 19, dubbed "the future of tennis", and his superior fitness told as he ground out a thrilling 4-6, 6-3, 6-7 (5/7), 6-3, 6-2 win
Serena Williams thumped dangerous Swiss teen Belinda Bencic 6-4, 6-3 to enter the second round of the Australian Open.
Andy Murray, who saved a match point, lost the first set to Milos Raonic but won the next two sets on tie-break to reach the final of the ATP World Tour Finals on Saturday
Andy Murray brushed aside Stan Wawrinka in 86 minutes at London's O2 Arena to ensure he finished top of his group in the ATP World Tour Finals and avoided a last four clash with Novak Djokovic
Rafael Nadal's 2016 season was plagued by physical problems and he cut his campaign short in October to recover fully to target a return to Grand Slam glory in 2017
Andy Murray will move to the top of men's tennis rankings for the first time in his career after replacing long-time incumbent Novak Djokovic