The 37-year-old Herman has never won on the PGA Tour and conceded that topping the leaderboard was "unexpected".
Herman's five-under-par round of 65 was enough to see him go one shot clear at the front, with compatriot Brendan Steele next best.
Three-time major winner Padraig Harrington, the 2005 Honda Classic champion, was a further shot adrift. Harrington is joined on three-under by Martin Flores and Patrick Reed.
World number one Rory McIlroy made a rocky return to action, carding a three-over round of 73.
The Ulsterman began in the worst possible fashion, losing his ball of the tee at the first as he registered a double bogey. After pulling a shot back at the third, McIlroy proceeded to bogey the fourth and notch up another double bogey at the fifth. A birdie at the eighth saw McIlroy take the turn in 38.
Further bogeys at 11 and 14 had McIlroy in further trouble, but birdies at 17 and 18 meant that he finished on three-over, eight shots off the pace set by Herman.