Both of Guthrie's goals come from free-kicks - the first unintended, as it flew through a packed Birmingham penalty area, and the second an accurate set-piece that found the net via a post.
Those goals helped Reading make it 13 points from their last five league games and leave Birmingham unable to cap a memorable week with a third successive victory.
Lee Clark's men beat Sheffield Wednesday 4-1 in the league last time out and then followed that up with a 3-1 cup win over Swansea, and buoyed by those successes they started brightly.
Jesse Lingard, the four-goal hero on debut against Wednesday, was again prominent with the on-loan Manchester United midfielder working industriously on the left flank.
However, Birmingham failed to capitalise on their early superiority and Reading responded with a series of swift breaks. Garath McCleary released Pavel Pogrebnyak inside the Birmingham area but the Russian's fierce shot was well saved by Darren Randolph.
Reading kept up the pressure and Chris Baird nodded powerfully over from a Guthrie corner.
McCleary also attempted an effort on goal from 20 yards, but Randolph did not have to deal with it as the shot trickled weakly wide. However, he did have to deal with McCleary's low cross soon after, scrambling on the floor with Hal Robson-Kanu and Adam Le Fondre before regaining control of the ball.
Reading's pressure finally paid off in the 32nd minute as they took the lead, albeit with a goal that was tinged with good fortune.
Chris Burke was penalised for handball and Guthrie's free-kick from wide on the left did not appear to carry too much danger. Yet it somehow found its way through a mass of bodies in the area and nestled in the far corner of Randolph's net.
Birmingham had been disappointing, barely mustering a threat in the first half, and they hardly improved after the interval. Reading took control again and could have extended their lead had referee James Adcock not intervened.
Pogrebnyak had won an aerial duel with Jonathan Spector and Adcock initially awarded Reading the advantage and waved play on.
But with Pogrebnyak, Le Fondre and McCleary bearing down on the thinly stocked Birmingham defence, Adcock stopped the game to allow Spector to receive treatment and halted Reading's progress.
At last Birmingham fashioned an opportunity, when Burke shot over from a David Murphy cross, but Reading were soon back on the attack. McCleary cut in from the left and drove wide but then was more accurate with a deflected effort that Randolph did well to push behind for a corner.
However, the Birmingham goalkeeper was beaten again in the 75th minute. Dan Burn fouled Robson-Kanu on the edge of the area and Guthrie curled home a fine free-kick via Randolph's near post to complete Reading's comfortable win.