Villas-Boas's side had won the first match of the Portuguese coach's reign when they beat League One club Wycombe 3-0 in a behind-closed-doors fixture in midweek, but this was a tougher test against battle-hardened Championship opposition.
It was also the first public outing for Villas-Boas's team since the 33-year-old arrived from Porto as successor to Carlo Ancelotti last month and a first-half own goal from former Chelsea defender Tal Ben Haim was enough to secure the victory.
Villas-Boas sent out completely different line-ups in each half as he gave all his players a chance to gain pre-season fitness ahead of their tour to Asia.
He chose to start the match with a blend of youth and experience, with the likes of Fernando Torres, Ashley Cole and Florent Malouda lining up alongside youngsters Billy Clifford and Tomas Kalas.
Portsmouth came close to breaking the deadlock within the opening three minutes when David Norris burst down the left flank and only a smart block from Cole prevented Dave Kitson flicking home at the near post.
But despite that flash of attacking intent, it was Chelsea who took the lead through a bizarre own goal from Ben Haim in the seventh minute.
A Torres cross from the right was scuffed by Greg Halford as he attempted to clear and Ben Haim then miscued his headed clearance into his own net.
Chelsea continued to press after taking the lead, with Torres somehow heading a glorious chance wide.
Despite Chelsea's dominance, Portsmouth mustered a few chances of their own and tested Ross Turnbull on several occasions.
The Chelsea goalkeeper was forced to stop Norris' bundled header sneaking home, before palming wide Luke Varney's thumping drive as half-time approached.
Villas-Boas made 11 changes at half-time as the likes of John Terry, Frank Lampard, Didier Drogba, Nicolas Anelka and Jose Bosingwa came on.
However, it was another Chelsea substitute -- goalkeeper Hilario -- who had the biggest impact as he brought down Varney and referee Keith Stroud awarded a penalty.
Varney took the spot-kick but was thwarted by a fine save from Hilario as the Portuguese stopper redeemed himself.
Hilario's save was nearly wasted after defensive miscommunication allowed Varney to burst through twice in quick succession, but Nathan Chalobah and Bosingwa's blushes were spared by last-ditch clearances on both occasions.
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