Bianconeri manager Maurizio Sarri made three changes, with talisman Cristiano Ronaldo making a return alongside Giorgio Chiellini, who was making his first start since August last year, and Blaise Matuidi.
Ronaldo found the back of the net in just the fifth minute of the match after turning home Paulo Dybala's cross at the back post but the goal was chalked off for offside.
SPAL were growing in the game after that, pinning back Juventus in their own half but they were not creating clear openings in the final third.
Ronaldo eventually broke the deadlock for Sarri's men in the last six minutes of the first stanza after beating the offside turn home from Juan Cuadrado's cross.
Juventus were turning up the heat early in the second stanza with a host of chances and Aaron Ramsey finally doubled their lead on the hour-mark with a chip over SPAL goalkeeper Etrit Berisha from Dybala's through ball.
The hosts were given a lifeline in the 66th minute after they were awarded a penalty for a challenge by substitute Matthijs De Ligt on Simone Missiroli inside the box following a Video Assistant Referee review Andrea Petagna stepped up and drilled home a low strike int the bottom corner.
Sarri needed fresh legs in midfield in the 73rd minute as Adrien Rabiot came on for Ramsey and while Federico Bernardeschi replaced Matuidi a few minutes later.
Ronaldo came close to restoring a two-goal cushion for Bianconeri with a free-kick from just outside the box in the last two minutes that hit the frame of the goal, with Berisha beaten.
In the end, Juventus held on to confirm a 2-1 win that extended their lead at the top of the log to four points over second-place Lazio and six ahead of Inter Milan who are third.