Former world number one Tiger Woods, making his first start since the Masters last month, endured a mixed day that included two double bogeys and two bogeys, but with five birdies signed for a first-round one-over 73.
Japan's Hideki Matsuyama, Canadian David Hearn and Americans Charley Hoffman and Kevin Na shared the lead on five-under 67 on a tightly bunched leaderboard in the US PGA Tour's $10 million flagship event at TPC Sawgrass in Florida.
McIlroy headed a group of 14 players on 69 that also included Australians Jason Day and Marc Leishman, and Spain's Sergio Garcia.
Northern Ireland's McIlroy played alongside Spieth and Day and held up his end in the ballyhooed budding rivalry with Masters champion Spieth, who struggled to a three-over 75.
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"I did feel sharp," said McIlroy, who arrived in Florida off a victory in the World Golf Championships Match Play in California on Sunday and celebrated his 26th birthday on Monday.
"It's about staying patient," said McIlroy, who teed off on 10 and made his first birdie at 15.
He promptly followed that with an eagle at the par-five 16th, where he landed his second shot within seven feet.
"There's a lot of pars on my round, but I was able to pick off a couple of birdies and a nice eagle on 16, so pleased with the start," McIlroy said.