The index closed 11.97 points lower after dropping 1.45 points in the previous session. It has fallen four sessions in a row.
Trading on the Ho Chi Minh Stock Exchange decreased by 15% to VND13.25 trillion (US$522 million).
The VN-30 basket, comprising the 30 largest capped stocks, saw 23 tickers fell.
BCM of Becamex Investment and Industrial Development led with a 4.5% decline, followed by FPT of IT giant FPT Corporation, down 3%.
GVR of Vietnam Rubber Group and MWG of electronics retail chain Mobile World both lost 2.4%.
Six blue chips gained, including VHM of property giant Vinhomes with a 3.4% rise.
Foreign investors were net sellers to the tune of VND1.66 trillion, mainly selling FPT and VHM.
The HNX-Index for stocks on the Hanoi Stock Exchange, home to mid and small caps, fell 0.95%, while the UPCoM-Index for the Unlisted Public Companies Market went down 1.46%.
Asian stocks rose on Tuesday while U.S. bond yields and the dollar hung back from multi-month highs as traders awaited President-elect Donald Trump's cabinet selection and sought to gauge the outlook for Federal Reserve easing, Reuters reported.
Tech shares advanced, tracking Wall Street's recovery from last week's steep losses, although Nvidia's upcoming earnings on Wednesday limited the scope for big moves.
Japan's Nikkei added 0.5%, while Australia's equity benchmark jumped 0.8% and reached a record high. Taiwanese shares advanced 1.3%.
Chinese markets were weak though, with investors mulling potential Trump tariffs and waiting on more details of stimulus from Beijing. Hong Kong's Hang Seng slipped 0.1%, reversing earlier gains, and mainland blue chips dropped 1.2%.