An inspection report published today finds that although the council had taken action to improve leadership since similarly critical findings in 2011, the impact had been "too limited".
"There are widespread and serious weaknesses in Slough's child protection service," the report states.
"As a result, children do not always receive the protection they need when they require it. Many children who are looked after by Slough do not do as well as they could in their education.
"In addition, services to help care leavers are seriously inadequate."
Slough is the first authority to be given a rating of inadequate under Ofsted's tougher new inspection framework.
Last week, the London Borough of Hillingdon was given a "requires improvement" rating, while Hartlepool and Derbyshire were both rated good.
Slough was previously inspected in May 2011, when, under the previous inspection framework, safeguarding arrangements were judged inadequate and the looked-after children's services were judged adequate.
The latest report found there had been insufficient progress in the development of multi-agency child protection work between the police and children's social care.
Inspectors also commented on the authority's inability to recruit enough qualified and suitably experienced permanent social workers. It discovered an "over-reliance on temporary staff" with a lot of work needing to be redone, "leading to delays and drift in many children's cases".
"As a result, nearly all social workers have excessively high caseloads", the report states. "In the majority of cases, they do not have sufficient time to spend with individual children to learn about their lives.
"This lack of knowledge often leads to poor quality assessments, plans and outcomes for children."
Jane Wood, director of wellbeing at Slough Council, said: "We accept the overall judgement of inadequate.
"This was not a surprise and was reflected in our own self-assessment. We were open with Ofsted and were aware we still had a way to go."
However, Wood claimed Ofsted had not taken into account many of the improvements the authority has made. "In some areas, we believe they have been unfair, inaccurate and disproportionate in their report of the issues", she said.
"They were also unable to take into account many improvements we have made which have not yet shown their impact.
"We are determined to make the improvements necessary. Our journey is ongoing and we do not want this to derail our progress."