Mattis said that United Nations -brokered negotiations to resolve the conflict in Yemen are needed.
The death toll was one of the largest in a single incident involving Saudi forces since a Saudi-led coalition intervened in Yemen's war in 2015 in support of President Abedrabbo Mansour Hadi's internationally recognised government in its fight against Iran-backed Houthi rebels.
US Defense Secretary Jim Mattis is in Saudi Arabia Wednesday to reinvigorate the Riyadh-Washington alliance, with both seeing a common adversary in Iran and its "destabilising" activities.
As he met Deputy Crown Prince and Defense Minister Mohammed bin Salman, Mattis appeared to allude to deteriorated relations during the Obama administration, which spearheaded a seven-nation nuclear deal with Iran that deeply upset the Saudis.
"Secretary Mattis began his trip with Saudi Arabia Tuesday, where he is scheduled to have a series of meetings with key worldwide counterparts in order to strengthen commitments to the US-Saudi security partnership", Johann Schmonsees, press attache at the US Embassy in Riyadh, told Arab News. Mattis commanded troops during the 2003 invasion of Iraq.
He said the USA would "reinforce Saudi Arabia's resistance to Iran's mischief" and suggested the possibility of President Donald Trump visiting Saudi Arabia.
The Sunni Muslim kingdom "felt marginalised" during global negotiations on a nuclear accord with Shiite Iran, an American defence official said.
Mattis said he plans to discuss the current security situation in the region and how the United States can "deepen and broaden" its relationship with Saudi Arabia.
He further asserted that his presence in Saudi Arabia could pave the way for a Trump visit to the monarchy, a long-time U.S. ally in the Middle East.
Trump's Yemen focus has so far been on a major escalation of attacks against jihadists from the Al-Qaeda in the Arabian Peninsula group in Yemen.
"We will have to overcome Iran's efforts to destabilise yet another country and create another militia in their image of Lebanese Hezbollah but the bottom line is we are on the right path for it", Mattis added. The coalition forces accuse Iran of trying to use the Houthis to expand its influence in Yemen, something the Iranians are denying.