Wales Under-20 ace Lewis starts in a front row that also contains Gethin Jenkins and Kristian Dacey for the fixture at the Peroni Stadium.
Williams hits his memorable milestone by playing his 100
th game in the number nine jersey and combines with Rhys Patchell at half back.
Head Coach Danny Wilson has named a powerful side that contains just two changes to the team that narrowly lost out to reigning Guinness PRO12 league champions Glasgow Warriors last weekend.
Rising star Lewis comes in at tighthead prop while the other change is a recall for former All Black lock Jarrad Hoeata into the second row to partner James Down.
USA international Blaine Scully also makes a welcome return among the replacements. Cam Dolan, Sam Hobbs and Josh Navidi both miss the European fixture due to injury.
Wilson said: “We’re looking forward to the European competition. It is another series of games to build on what we are improving on and the lessons we have learnt from the league.
“Calvisano away is a challenge similar to Zebre away and we have got to face it better than we did last time.
“After that we have Harlequins at home with a short turnaround; we have some huge games coming up.
“We are looking no further than Calvisano in this competition and building on our performance with each week,” he added.
“We need to build momentum as we look to a big two months and the festive derby games coming up too. The games are coming thick and fast and we’ve got to approach each one with the same detail.”
Cardiff Blues: 15 Dan Fish, 14 Alex Cuthbert, 13 Rey Lee-Lo, 12 Gavin Evans, 11 Tom James, 10 Rhys Patchell, 9 Lloyd Williams; 1 Gethin Jenkins (c), 2 Kristian Dacey, 3 Dillon Lewis, 4 Jarrad Hoeata, 5 James Down, 6 Ellis Jenkins, 7 Sam Warburton, 8 Josh Turnbull
Replacements: 16 Matthew Rees, 17 Thomas Davies, 18 Craig Mitchell, 19 Lou Reed, 20 Manoa Vosawai, 21 Tavis Knoyle, 22 Jarrod Evans, 23 Blaine Scully