The Commons education select committee said that national targets should be scrapped in favour of a system where schools set their own goals based on individual pupils' ability.
In a report on pupil achievement in secondary schools, published this week, the committee also criticises the Government's key stage 3 strategy as "lacking the clear focus found in the primary phase".
The committee's attack on the amount of testing comes despite a determined defence of the regime by David Miliband, schools standards minister.
It shows the strength of feeling over the issue within the Labour party and bolsters the position of the National Union of Teachers, which has promised to ballot members over a boycott of national tests at age seven, 11 and 14.
Barry Sheerman, chairman of the committee, accused ministers of "testing schools to distraction".
He said: "National target setting has gone as far as it can go. It is time we moved from a top-down to a bottom-up approach."
John Bangs, NUT head of education, described the report as "refreshing". He said the committee should take the next step and call for an overhaul of the entire testing regime.
Charles Clarke, Education Secretary, said: "Scrapping targets would let children down, particularly many from poorer backgrounds, where targets can help to break down a culture of low expectation."
The report is critical of the number of government initiatives aimed at secondary schools, saying that their purpose and impact are unclear.
It urges ministers to carry out a proper assessment of the effectiveness of its flagship Excellence in Cities scheme, intended to help pupils in deprived areas. Previous schemes such as education action zones have been introduced and then halted without a proper evaluation of their effectiveness, it says.
The committee also calls on the Government to do more to tackle poverty - "unarguably" the biggest cause of low achievement - and to do more to address the lack of books and other educational resources in the homes of children from deprived backgrounds.
League tables should be reformed so that they distinguish between low achievement and underachievement. Some low-achieving pupils and schools may be reaching their potential while some high achievers are underperforming, it says.