Pence and his wife Karen visited the wall separately as required by the ultra-Orthodox Jewish authorities who govern the site under strict interpretation of religious law.
The vice president, wearing a black skullcap, inserted a piece of paper inside a crack in the ancient wall's stones in accordance with the tradition of leaving a prayer.
He then placed his right hand on the wall before stepping backwards and gazing at the site for a few moments and signing the guest book.
"Very inspiring," Pence said after leaving.
The Western Wall is among the last remnants of the second Jewish temple destroyed by the Romans in 70 AD.
It lies in east Jerusalem, occupied by Israel in the Six- Day War of 1967 and later annexed in a move never recognised by the international community.
Many Israelis are likely to interpret the Western Wall visit as Pence further backing their claim over the entire city.
Since arriving on Sunday, Pence has repeatedly reaffirmed Trump's December 6 declaration of Jerusalem as Israel's capital, though he has reiterated that the final borders must be negotiated.
The Palestinians have been deeply angered by the declaration and are boycotting Pence's visit.
Israel claims all of Jerusalem as its capital, while the Palestinians see the eastern sector as the capital of their future state.
The US move to recognise Jerusalem as Israel's capital broke with decades of international consensus that the city's status should be settled as part of a two-state peace deal between Israel and the Palestinians.
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