Ryder is 12-under-par 204 through three rounds in San Diego after shooting an even-par 72 on Friday at the South Course at Torrey Pines for a two-shot lead.
But hot in pursuit is second-placed Jon Rahm (66-206) and third placed Tony Finau, who enjoyed a 64 for the round of the day and is now just four behind.
Ryder had a three-stroke lead on the field entering the third round and limited his mistakes while missing opportunities to extend his edge.
After a bogey at the par-4 second hole and a birdie at the par-5 sixth, the 33-year-old parred his final 12 holes.
He couldn't capitalise on any of the three remaining par-5 holes, missing an 8-foot birdie putt at No.13 and an 11-footer on the 18th. He also missed an 11-foot birdie try at the par-4 14th.
"Today it's just a different level of pressure," Ryder said. "I didn't feel like I had to go try and make something happen or press, you know, so I didn't panic when I made a bogey on 2 and I kind of just adjusted to the round and kind of got a feel for where I was at with my swing and my game.
"Hit some really good shots, felt like I could have made a couple more putts, but overall I'm very pleased."
Rahm did one better than his second-round 67. After playing the first five holes in even par, he went 5 under over the next four with three straight birdies and a 12-foot eagle putt at the par-5 ninth.
The world No.3 added another mid-range birdie putt at No.15 while avoiding bogey the rest of the way.
"Goal is to catch up as much as possible," Rahm said. "I was eight shots (behind Ryder) starting the day, hopefully it's only two starting tomorrow."
Should Rahm overtake Ryder and win Saturday, he will be the first player to win three straight PGA Tour starts since Dustin Johnson in 2017 after winning the Sentry Tournament of Champions in Maui and The American Express.
Finau started his round on the back nine and made the turn in enviable fashion. Following consecutive birdies at Nos.17 and 18, he holed out from the fairway at No.1 for an eagle 2.
"It helps when you hole out," Finau said. "That was really exciting. That's when the round kind of got my attention, the juices started to flow a little bit as I was making kind of a run there."
Tied for fourth at 7 under are Sungjae Im of South Korea (67), Collin Morikawa (70), Max Homa (71) and Sahith Theegala (71).
Jason Day (73) at four under is in a tie for 15th. The former world No.1 is the only Australian heading into the weekend after Aaron Baddeley (71,74) missed the even-par cut by one.
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