Mahomes now has 13 touchdown passes without an interception, breaking the NFL record for TD passes in the first three weeks of a season. Peyton Manning threw 12 to start the 2013 campaign.
Mahomes' touchdown passes to Conley - Harris and Watkins , along with a pair of TD runs by Kareem Hunt, helped Kansas City (3-0) race to a 35-7 lead late in the first half.
Few leads are safe against the Chiefs' porous defense, though.
The 49ers (1-2) rallied behind running backs Matt Breida and Alfred Morris, who kept gouging the Chiefs' defensive front, and Jimmy Garopolo who threw for 251 yards and 2 scores . It was Garoppolo's 11-yard pass to Marquis Goodwin early in the third quarter that started the comeback, and Morris scored on a short touchdown run later in the quarter to make it 35-24.
After the Chiefs tacked on a field goal early in the fourth to extend their lead, the 49ers came back with a grinding, 17-play drive that wiped out more than half the period. But it ended in a strange sequence that began with Garoppolo taking a hard hit from Steven Nelson along the sideline. Garoppolo easily could have stepped out of bounds, but instead he was crushed on his throwing shoulder and had to leave.
C.J. Beathard came in and threw what appeared to be a fourth-down touchdown pass to George Kittle, but it was wiped out by offensive pass interference.
There was only 5:17 left, but rather than go for it on fourth-and-goal at the Kansas City 25, 49ers coach Kyle Shanahan elected to kick a field goal -- keeping it a two-possession game.
San Francisco proceeded to kick it deep rather than try an onside kick. The Chiefs picked up a first down on a penalty, and Hunt churned his way for two more first downs to put the game away.