She attended Crescent Girls' School and National Junior College—where she became one of the top students for the A Level examinations in her cohort and was named Student of the Year,[3] before graduating from the University of Singapore (now the National University of Singapore) in 1976 with a Bachelor of Engineering with first class honours degree in electrical engineering.

Ho joined Singapore Technologies in 1987 as deputy director of engineering and took on various senior responsibilities before becoming its president and chief executive officer in 1997.

[8] For her public service, she was conferred the Ho has appeared in many rankings of the most powerful and influential people in the world.

[13] In 2007, Forbes magazine ranked her 3rd in its annual list of the world's most powerful women, behind German Chancellor Angela Merkel and China's Vice-Premier Wu Yi.

The annual Asia House award recognises individuals who embody the 'Servant Leader' – economic success and professional excellence accompanied by moral leadership and service to society.

She is the patron of Assisi Hospice, and the founding chairman of Trailblazer Foundation Ltd, an IPC charity which provides funding for education, health, sports and community welfare.

[3] In August 2016, Ho received a positive reception[22] when on a state visit to the White House to mark 50 years of bilateral relations between the US and Singapore,[23] she carried a pouch designed by an autistic student from Pathlight School (under its Artist Development Program).

[30] She met her husband, Lee Hsien Loong, the eldest son of former Singapore Prime Minister Lee Kuan Yew, while starting out in her career at the Ministry of Defence together with former prime minister Goh Chok Tong.

Ho is an active social media user and regularly shares her views and interacts with others on Facebook.

[46][47] On 11 April 2020, Ho shared an article on Facebook about Taiwan’s donation of masks to Singapore with the following caption: "Errr".

[48] In August 2023, amidst public debate over then-presidential candidate Tan Kin Lian's posts about 'pretty girls', Ho shared her views on Facebook, suggesting that the Presidential Elections Committee should not be expected to be the "arbiter of moral standards" and that "[m]aybe TKL had asked for permission to take the pictures or to post".